Three important enzymes required for brain monoamine neurotransmitter synthesis are tyrosine hydroxylase, tryptophan hydroxylase and dopamine-beta-hydroxylase. These three enzymes were measured as a function of age in various brain regions in spontaneously hypertensive rats (SHR) and stroke prone substrain (SHR-SP), and control Wistar-Kyoto rats (WKR). There appear to be transient increases in the content of tyrosine hydroxylase in the striatum and hypothalamus of the SHR and SHR-SP between 3 and 8 weeks of age. Likewise there are small increases in dopamine-beta-hydroxylase in the hypothalamus, thalamus and pons-medulla. The most significant increase appears to be in the hypothalamus at 5 weeks of age. Changes in hypothalamic dopamine-beta-hydroxylase appear to correlate well with the tendency to develop hypertension. Small increases in hypothalamic tryptophan hydroxylase are also seen in the SHR and SHR-SP. Because of the early and transient nature of the changes in brain neurotransmitter synthetic enzymes it is suggested that malfunction of one or more of the brain monoamine systems may be an early event in the development of hypertension in these rat models. BIBLIOGRAPHIC REFERENCES: Nagaoka, A. and Lovenberg, W.: Plasma norepinephrine and dopamine-beta-hydroxylase in genetic hypertensive rats. Life Sci. 19: 29-34, 1976. Nagaoka, A. and Lovenberg, W.: Regional changes in the activities of aminergic biosynthetic enzymes in the brains of hypertensive rats. European J. of Pharmacology 43: 297-306, 1977.